Sporadic and Familial Hemiplegic Migraine: Diagnosis and Treatment

ABSTRACT

Hemiplegic migraine is a rare subtype of migraine with aura associated with transient hemiplegia. The weakness is caused by motor aura. Hemiplegic migraine is the only headache syndrome associated with known genetic mutations and serves as a model for understanding more common varieties of migraine. Because the phenotype includes striking yet transient neurological signs and symptoms, it is imperative that clinicians know the differential diagnosis to rule out possible secondary etiologies when treating patients with hemiplegic spells. Hemiplegic migraine occurs with equal prevalence in either a sporadic or familial form differentiated only by family history. Thus far, treatment trials are anecdotal, although verapamil and acetazolamide have shown promise.

KEYWORDS

Familial hemiplegic migraine - sporadic hemiplegic migraine - migraine genetics

REFERENCES

• 1 Liveing E. On Megrim, Sick-Headache, and Some Allied Disorders. London; Churchill 1873
• 2 Whitty C WM. Familial hemiplegic migraine.  J Neurol Neurosurg Psychiatry. 1953;  16 172-177
• 3 Headache Classification Committee of the International Headache Society . The international classification of headache disorders.  Cephalalgia. 2004;  24 28-29
• 4 Thomsen L L, Eriksen M K, Roemer S F et al.. An epidemiological survey of hemiplegic migraine.  Cephalalgia. 2002;  22 361-375
• 5 Ducros A, Denier C, Joutel A et al.. The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel.  N Engl J Med. 2001;  345 17-24
• 6 Thomsen L L, Eriksen M K, Roemer S F, Andersen I, Oleson J, Russell M B. A population-based study of familial hemiplegic migraine suggests revised diagnostic criteria.  Brain. 2002;  125 1379-1391
• 7 Bradshaw P, Parsons M. Hemiplegic migraine, a clinical study.  Q J Med. 1965;  34 65-86
• 8 Thomsen L L, Ostergaard E, Olesen J, Russell M B. Evidence for a separate type of migraine with aura.  Neurology. 2003;  60 595-601
• 9 Terwindt G, Kors E, Haan J et al.. Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine.  Arch Neurol. 2002;  59 1016-1018
• 10 Beauvais K, Cave-Riant F, De Barace C, Tardieu M, Tournier-Lasserve E, Furby A. New CACNA1A gene mutation in a case of familial hemiplegic migraine with status epilepticus.  Eur Neurol. 2004;  52 58-61
• 11 Razavi M, Razavi B, Fattal D, Afifi A, Adams H. Hemiplegic migraine induced by exertion.  Arch Neurol. 2000;  57 1363-1365
• 12 Black D F, Kung S, Sola C L, Bostwick J M, Swanson J W. Familial hemiplegic migraine, neuropsychiatric symptoms, and Erdheim-Chester disease.  Headache. 2004;  44 911-915
• 13 Kors E E, Terwindt G M, Vermeulen F L et al.. Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine.  Ann Neurol. 2001;  49 753-760
• 14 Ophoff R A, Terwindt G M, Vergouwe M N et al.. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4 .  Cell. 1996;  87 543-552
• 15 Elliott M A, Peroutka S J, Welch S, May E F. Familial hemiplegic migraine, nystagmus, and cerebellar atrophy.  Ann Neurol. 1996;  39 100-106
• 16 Spadaro M, Ursu S, Lehmann-Horn F et al.. A G301R Na/K+-ATPase mutation causes familial hemiplegic migraine type 2 with cerebellar signs.  Neurogenetics. 2004;  5 177-185
• 17 Haan J, Terwindt G M, Ophoff R A et al.. Is familial hemiplegic migraine a hereditary form of basilar migraine?.  Cephalalgia. 1995;  15 477-481
• 18 Ambrosini A, D'Onofrio M, Grieco G S et al.. A new mutation on the ATP1A2 gene in one Italian family with basilar-type migraine linked the FHM2 locus.  Neurology. 2005;  64(suppl) A132
• 19 Wada T, Kobayashi N, Takahashi Y, Aoki T, Watanabe T, Saitoh S. Wide clinical variability in a family with a CACNA1A T666M mutation: hemiplegic migraine, coma, and progressive ataxia.  Pediatr Neurol. 2002;  26 47-50
• 20 Carrera P, Piatti M, Stenirri S et al.. Genetic heterogeneity in Italian families with familial hemiplegic migraine.  Neurology. 1999;  53 26-33
• 21 Joutel A, Bousser M G, Biousse V et al.. A gene for familial hemiplegic migraine maps to chromosome 19.  Nat Genet. 1993;  5 40-45
• 22 Ducros A, Joutel A, Vahedi K et al.. Mapping of a second locus for familial hemiplegic migraine to 1q21-q23 and evidence of further heterogeneity.  Ann Neurol. 1997;  42 885-890
• 23 Gardner K, Barmada M M, Ptacek L J, Hoffman E P. A new locus for hemiplegic migraine maps to chromosome 1q31.  Neurology. 1997;  49 1231-1238
• 24 De Fusco M, Marconi R, Silvestri L et al.. Haploinsufficiency of ATP1A2 encoding the Na⁺/K⁺ pump alpha2 subunit associated with familial hemiplegic migraine type 2.  Nat Genet. 2003;  33 192-196
• 25 Estevez M, Gardner K L. Update on the genetics of migraine.  Hum Genet. 2004;  114 225-235
• 26 Dichgans M, Freilinger T, Eckstein G et al.. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.  Lancet. 2005;  366 371-377
• 27 Giffin N J, Benton S, Goadsby P J. Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A mutation.  Dev Med Child Neurol. 2002;  44 490-493
• 28 Alonso I, Barros J, Tuna A et al.. Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family.  Arch Neurol. 2003;  60 610-614
• 29 Vanmolkot K R, Kors E E, Hottenga J J et al.. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions.  Ann Neurol. 2003;  54 360-366
• 30 Bassi M T, Bresolin N, Tonelli A et al.. A novel mutation in the ATP1A2 gene causes alternating hemiplegia of childhood.  J Med Genet. 2004;  41 621-628
• 31 Van den Maagdenberg A M, Pietrobon D, Pizzorusso T et al.. A CACNA1A knockin migraine mouse model with increased susceptibility to cortical spreading depression.  Neuron. 2004;  41 701-710
• 32 Lauritzen M. Pathophysiology of the migraine aura: the spreading depression theory.  Brain. 1994;  117 199-210
• 33 Mullner C, Broos L AM, Van den Maagdenberg A M, Striessnig J. Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V16961 alter C_AV2.1 Ca2+ channel gating.  J Biol Chem. 2004;  279 51844-51850
• 34 Dichgans M, Herzog J, Freilinger T, Wilke M, Auer D P. ¹H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1.  Neurology. 2005;  64 608-613
• 35 Berg M J, Williams L S. The transient syndrome of headache with neurologic deficits and CSF lymphocytosis (review).  Neurology. 1995;  45 1648-1654
• 36 Parikh S, Swaiman K F, Kim Y. Neurologic characteristics of childhood lupus erythematosus.  Pediatr Neurol. 1995;  13 198-201
• 37 Seleznick M J, Silveira L H, Espinoza L R. Avascular necrosis associated with anticardiolipin antibodies.  J Rheumatol. 1991;  18 1416-1417
• 38 Bartleson J D, Krecke K N, O'Neill B P, Brown P D. Reversible, strokelike migraine attacks in patients with previous radiation therapy.  Neuro-oncol. 2003;  5 121-127
• 39 Koo B, Becker L, Chuang S et al.. Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological and genetic observations.  Ann Neurol. 1993;  34 25-32
• 40 Steele J G, Nath P U, Burn J, Porteous M E. An association between migrainous aura and hereditary haemorrhagic telangiectasia.  Headache. 1993;  33 145-148
• 41 de Grauw T J, Smit L M, Brockstedt M, Meijer Y, vd Klei-von Moorsel J, Jakobs C. Acute hemiparesis as the presenting sign in a heterozygote for ornithine transcarbamylase deficiency.  Neuropediatrics. 1990;  21 133-135
• 42 Silva G S, Almeida C M, Felix E P, Fukujima M M, Ferraz H B, Gabbai A A. Cerebral venous thrombosis and homocystinuria: case report.  Arq Neuropsiquiatr. 2001;  59 815-816
• 43 Dora B, Balkan S. Sporadic hemiplegic migraine and Sturge-Weber syndrome.  Headache. 2001;  41 209-210
• 44 Yu W, Horowitz S H. Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.  Neurology. 2003;  60 120-121
• 45 Fuentes B, Diez Tejedor E, Pascual J, Coya J, Quirce R. Cerebral blood flow changes in pseudomigraine with pleocytosis analyzed by single photon emission computed tomography: a spreading depression mechanism?.  Cephalalgia. 1998;  18 570-573
• 46 De Benedittis G, Ferrari Da Passano C, Granata G, Lorenzetti A. BF changes during headache-free periods and spontaneous/induced attacks in migraine with and without aura: a TCD and SPECT comparison study.  J Neurosurg Sci. 1999;  43 141-147
• 47 Pascual J, Valle N. Pseudomigraine with lymphocytic pleocytosis.  Curr Pain Headache Rep. 2003;  7 224-228
• 48 Vahedi K, Denier C, Ducros A et al.. CACANA1A gene de novo mutation causing hemiplegic migraine, coma, and cerebellar atrophy.  Neurology. 2000;  55 1040-1042
• 49 Chapman K M, Szczygielski B I, Toth C et al.. Pseudomigraine with lymphocytic pleocytosis: a calcium channelopathy? Clinical description of 10 cases and genetic analysis of the familial hemiplegic migraine gene CACNA1A .  Headache. 2003;  43 892-895
• 50 Crawford J S, Konkol R J. Familial hemiplegic migraine with crossed cerebellar diaschisis and unilateral meningeal enhancement.  Headache. 1997;  37 590-593
• 51 Hayashi R, Tachikawa H, Watanabe R, Honda M, Katsumata Y. Familial hemiplegic migraine with irreversible brain damage.  Intern Med. 1998;  37 166-168
• 52 Oberndorfer S, Wober C, Nasel C et al.. Familial hemiplegic migraine: follow-up findings of diffusion-weighted magnetic resonance imaging (MRI), perfusion-MRI [99mTc] HMPAO-SPECT in a patient with prolonged hemiplegic aura.  Cephalalgia. 2004;  24 533-539
• 53 Lindahl A J, Allder S, Jefferson D, Allder S, Moody A, Martel A. Prolonged hemiplegic migraine associated with unilateral hyperperfusion on perfusion weighted magnetic resonance imaging.  J Neurol Neurosurg Psychiatry. 2002;  73 202-203
• 54 Barbour P J, Castaldo J E, Shoemaker E I. Hemiplegic migraine during pregnancy: unusual magnetic resonance appearance with SPECT scan correlation.  Headache. 2001;  41 310-316
• 55 Fitzsimons R B, Wolfenden W H. Migraine coma: meningitic migraine with cerebral oedema associated with a new form of autosomal dominant cerebellar ataxia.  Brain. 1985;  108 555-577
• 56 Lachance D H, Black D F, Bartleson J D. SMART: strokelike migraine attacks after radiation therapy.  Neurology. 2005;  64(suppl) A220
• 57 Arzimanoglou A, Aicardi J. The epilepsy of Sturge-Weber syndrome: clinical features and treatment in 23 patients.  Acta Neurol Scand Suppl. 1992;  140 18-22
• 58 Klapper J, Mathew N, Nett R. Triptans in the treatment of basilar migraine and migraine with prolonged aura.  Headache. 2001;  41 981-984
• 59 Prendes J L. Consideration on use of propranolol in complicated migraine.  Headache. 1980;  20 93-95
• 60 Gilbert G J. An occurrence of complicated migraine during propranolol therapy.  Headache. 1982;  22 81-83
• 61 Lastimosa A C. Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.  Neurology. 2003;  61 721-722
• 62 Dobrev D, Milde A S, Andreas K, Ravens U. The effects of verapamil and diltiazem on N-, P- and Q-type channels mediating dopamine release in rat striatum.  Br J Pharmacol. 1999;  127 576-582
• 63 Tricarico D, Barberi M, Camerino D C. Acetazolamide opens the muscular KCa2+ channel: a novel mechanism of action that may explain the therapeutic effect of the drug in hypokalemic periodic paralysis.  Ann Neurol. 2000;  48 304-312
• 64 Athwal B S, Lennox G G. Acetazolamide responsiveness in familial hemiplegic migraine.  Ann Neurol. 1996;  40 820-821
• 65 Kors E E, Haan J, Giffin N J et al.. Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine.  Arch Neurol. 2003;  60 684-688
• 66 Battistini S, Stenirri S, Piatti M et al.. A new CACNA1A gene mutation in acetazolamide-responsive familial hemiplegic migraine and ataxia.  Neurology. 1999;  53 38-43
• 67 Haan J, Sluis P, Sluis L H, Ferrari M D. Acetazolamide treatment for migraine aura status.  Neurology. 2000;  55 1588-1589
• 68 Weller M, Dichgans J, Klockgether T. Acetazolamide-responsive migraine in CADASIL.  Neurology. 1998;  50 1505
• 69 Yabe I, Sasaki H, Yamashita I, Takei A, Tashiro K. Clinical trial of acetazolamide in SCA6, with assessment using the Ataxia Rating Scale and body stabilometry.  Acta Neurol Scand. 2001;  104 44-47
• 70 Kaube H, Herzog J, Kaufer T, Dichgans M, Diener H C. Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine.  Neurology. 2000;  55 139-141
• 71 Centonze V, Brucoli C, Macinagrossa G, Attolini E, Camponozzi F, Albano O. Non-familial hemiplegic migraine responsive to naloxone.  Cephalalgia. 1983;  3 125-127
• 72 Tobita M, Hino M, Ichikawa N, Takase S, Ogawa A. A case of hemiplegic migraine treated with flunarizine.  Headache. 1987;  27 487-488
• 73 Rozen T. Treatment of a prolonged migrainous aura with intravenous furosemide.  Neurology. 2000;  55 732-733
• 74 Rozen T. Aborting a prolonged migrainous aura with intravenous prochlorperazine and magnesium sulfate.  Headache. 2003;  43 901-903